Dscam結合特性の膨大なレパートリーは,変数Igドメインのモジュール相互作用から生じる
Woj M Wojtowicz1, Wei Wu, Ingemar Andre
1Department of Biological Chemistry, Howard Hughes Medical Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095-1662, USA.
Cell
|September 25, 2007
まとめ
ドロソフィラ・ダウン症候群の細胞粘着分子 (DSCAM) の同型は,高度に特異的な自己結合を示し,ユニークなニューロン識別を可能にします. この広大な結合レパートリーは,回路形成中にニューロンが自己と非自己を区別することを保証します.
科学分野:
- 分子生物学は分子生物学である.
- 神経科学は神経科学である.
- 遺伝学 遺伝学とは
背景:
- ダウン症候群の細胞粘着分子 (Dscam) タンパク質は,ドロソフィラの神経回路の発達に不可欠です.
- Dscamの代替スプライシングは,多様な細胞外ドメインを持つ膨大な数のアイソフォームを生成します.
研究 の 目的:
- 多数のドロソフィラ・DSCAM同型体の結合特性を調査する.
- Dscamイソフォームがイソフォーム固有の同性愛結合を示すかどうかを判断する.
- Dscamの自己結合の構造的基盤を特定するために.
主な方法:
- 高通量ELISAベースの結合測定法の開発.
- 大量のDscamイソフォームの結合相互作用のテスト.
主要な成果:
- 試験されたDscamイソフォームの95%以上は,イソフォーム特有の同性愛結合を示した.
- 3つの変数免疫グロブリンドメインのそれぞれが,対極の異形体における対応ドメインと結合する.
- この自己結合を媒介する構造的要素が特定されました.
結論:
- Dscamのアイソフォームは自己結合ドメインを介して組み合わされ,同性愛結合タンパク質の大きなファミリーを作成します.
- Dscam認識分子の広範なレパートリーは,ユニークなニューロンアイデンティティとホモタイプ特異性を提供する可能性が高い.
- このメカニズムは,神経のプロセスが自己と非自己を区別することを可能にします.
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